Malignant transformation is accompanied by extensive alterations in the cell surface mosaic. This project employs immunological techniques in the study of spatial and temporal aspects of surface antigen expression during chemically-induced hepatocarcinogenesis in rats. We have raised a number of monoclonal antibodies to tissue-specific, stage-specific, tumor-associated, and differentiation antigens of normal adult and fetal hepatocytes, oval cells, regenerating liver cells, and hepatocellular carcinoma cells. To date, we have identified three novel antigens expressed by all hepatocellular carcinoma cells but not by normal or regenerating adult or fetal hepatocytes. One of these, tentatively identified as a receptor for transferrin, is expressed on foci of cells appearing within a few weeks of carcinogen exposure, and persists through the appearance of frank malignancy. This antibody appears to identify cells with a high risk of progression to malignancy. We have also produced a panel of monoclonal antibodies to oval cells, putavite transitional cells which proliferate in response to many hepatocarcinogens. Using these antibodies, we can phenotypically describe three oval cell subsets. Efforts are currently underway to use the antibodies, in conjunction with fluorescence-activated cell sorting, to isolate altered cells from livers of carcinogen-treated rats for transplantation into untreated recipients in order to identify the target cells of chemical hepatocarcinogens. (CS)